This invention relates to adhesive formulations derived from bioadhesive polyphenolic proteins which are useful in biomedical applications and which are particularly well suited for use in aqueous environments. Bioadhesive polyphenolic proteins, originally derived from several species of the mussel genus Mytilus, can be derived either from natural sources or be manufactured synthetically, and contain one or more sequences of repeating decapeptides having the formula: ##STR2## wherein each X is independently selected from the group comprising hydroxyl and hydrogen; and wherein each R is independently selected from the group comprising hydrogen and methyl. As used in this application, the term "bioadhesive polyphenolic proteins" is to be understood as referring to mixtures of proteins containing from about 10 to about 400, preferably from about 50 to about 150, units of the above repeating decapeptides, and optionally may contain other proteinaceous units, and chain extenders. Molecular weight is a key property of these adhesives. As shown in the examples, the unpolymerized decapeptide oligomer is not suitable for use, per se, as an adhesive because sufficient curing cannot be effected to form strong bonds. Ultimately, the adhesive, after curing, exhibits an adhesive strength of at least about 100 gm/cm.sup.2 when used on soft tissue, preferably at least about 150 gm/cm.sup.2, which indicates that a sufficient amount of intermolecular bonds and bonding between the substrate and the adhesive has been achieved to adhere the substrate to the adhesive.
Naturally-occurring protein from which the bioadhesive polyphenolic protein may be derived is produced and stored in the exocrine phenol gland of the mussel and is deposited onto marine surfaces by the mussel's foot during the formation of new adhesive plaques. Decapeptides may be obtained from the bioadhesive polyphenolic proteins by the method described by Waite in Journal of Biological Chemistry 258, 2911-15 (1983), and in U.S. Pat. No. 4,585,585. Additionally, the bioadhesive polyphenolic proteins may be obtained by genetic engineering techniques, well known to those skilled in the art.
Bioadhesive polyphenolic proteins exhibit excellent adhesive properties on a variety of surfaces, particularly surfaces submerged in water. The repeating decapeptides of the bioadhesive polyphenolic protein, are in essence the building blocks for a potentially wide variety of adhesive and coating substances.
The decapeptides and the bioadhesive polyphenolic proteins containing them show great promise for the development of commercial products. Virtually all prior art adhesives perform optimally when first applied on clean, dry surfaces. However, even those adhesives which display water resistant characteristics after curing, for example, resorcinolformaldehyde polymers, fail if applied in excessively moist environments. Bioadhesive polyphenolic proteins and their constituent decapeptides, on the other hand, have the potential to impart water-compatible characteristics to any adhesive formulation through their increased monomeric molecular weight, reduced tendency to diffuse from the application site, and increased number and variety of reactive residues, such as the "phenol-like" residues tryosine and dopa, that are especially capable of displacing water.
However, to date no compositions containing bioadhesive polyphenolic proteins have been available for scientific, medical or commercial use.
Accordingly, it is a principal object of this invention to provide compositions derived from bioadhesive polyphenolic proteins for use in various applications involving the need for adhesion in at least a partially aqueous environment, which applications specifically include, but are not limited to, medicine and surgery, botany, dentistry, underwater applications, chromatography, and the like.